Project Abstract HIV infection is associated with an increased risk of chronic kidney disease (CKD). Little is known about the contribution of HIV and antiretroviral therapy (ART) to CKD in asymptomatic HIV. We hypothesize that immediate initiation of ART in patients with high CD4+ cell counts will result in early improvements in clinically relevant markers of CKD, but that the early renal benefits will be partially offset by prolonged exposure to current first-line ART regimens with established nephrotoxic potential. We will test this hypothesis in an ancillary study to the Strategic Timing of AntiRetroviral Treatment (START) trial, a randomized trial investigating the impact of early versus deferred ART in treatment-nave individuals with CD4 > 500 cells/mm3. The randomized design of START offers a unique opportunity to directly compare the change in kidney function and markers of kidney injury between HIV-infected individuals who initiate ART immediately at high CD4 and similar individuals in whom ART is deferred. The prospective documentation of estimated glomerular filtration rate and availability of archived plasma and urine specimens will allow us to evaluate the impact of immediate ART on clinically relevant CKD outcomes and to refine existing risk scores for the prediction of CKD in HIV-positive individuals with high CD4.